PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.
Version 1
: Received: 28 March 2024 / Approved: 28 March 2024 / Online: 28 March 2024 (12:52:54 CET)
How to cite:
Mandal, M.; Pires, D.; Calado, M.; Azevedo-Pereira, J.M.; Anes, E. Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.. Preprints2024, 2024031773. https://doi.org/10.20944/preprints202403.1773.v1
Mandal, M.; Pires, D.; Calado, M.; Azevedo-Pereira, J.M.; Anes, E. Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.. Preprints 2024, 2024031773. https://doi.org/10.20944/preprints202403.1773.v1
Mandal, M.; Pires, D.; Calado, M.; Azevedo-Pereira, J.M.; Anes, E. Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.. Preprints2024, 2024031773. https://doi.org/10.20944/preprints202403.1773.v1
APA Style
Mandal, M., Pires, D., Calado, M., Azevedo-Pereira, J.M., & Anes, E. (2024). Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.. Preprints. https://doi.org/10.20944/preprints202403.1773.v1
Chicago/Turabian Style
Mandal, M., José Miguel Azevedo-Pereira and Elsa Anes. 2024 "Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-driven Cytotoxic Effects on HIV-Infected Cells during Coinfection." Preprints. https://doi.org/10.20944/preprints202403.1773.v1
Abstract
Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in acti-vating the perforin/granzyme cytotoxic pathways. It is targeted to the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CtsF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, we revealed a strong upregulation of CstF during infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA si-lencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. Here, we investigate the impact of CstF depletion during coinfection of Mtb-infected mac-rophages with lymphocytes infected with HIV. Our results indicate that decreasing CstF released by phagocytes impacts the major pro-granzyme convertase cathepsin C of cytotoxic immune cells. Consequently, an observed increase of the granzyme B apoptotic effects leads to a significant re-duction in viral replication in HIV-infected lymphocytes. Overall, our results indicate a mecha-nism of Mtb/HIV evasion of the cytotoxic mediated pathogen killing driven by the ax-is CstF/ catC/granzymes contributing to this syndemic interaction. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF.
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
